Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control
Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/145609 |
| _version_ | 1811076162111143936 |
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| author | Shalek, Alex Love, John Berger, Bonnie |
| author2 | Koch Institute for Integrative Cancer Research at MIT. Laboratory for Multiscale Regenerative Technologies |
| author_facet | Koch Institute for Integrative Cancer Research at MIT. Laboratory for Multiscale Regenerative Technologies Shalek, Alex Love, John Berger, Bonnie |
| author_sort | Shalek, Alex |
| collection | MIT |
| description | Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB. |
| first_indexed | 2024-09-23T10:17:18Z |
| format | Article |
| id | mit-1721.1/145609 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:17:18Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1456092024-03-20T19:46:09Z Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control Shalek, Alex Love, John Berger, Bonnie Koch Institute for Integrative Cancer Research at MIT. Laboratory for Multiscale Regenerative Technologies Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Institute for Medical Engineering & Science Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB. 2022-09-28T17:37:57Z 2022-09-28T17:37:57Z 2022 2022-09-28T17:23:33Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/145609 Shalek, Alex, Love, John and Berger, Bonnie. 2022. "Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control." Immunity, 55 (5). en 10.1016/J.IMMUNI.2022.04.004 Immunity Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Shalek, Alex Love, John Berger, Bonnie Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title | Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title_full | Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title_fullStr | Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title_full_unstemmed | Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title_short | Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| title_sort | multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control |
| url | https://hdl.handle.net/1721.1/145609 |
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